Polo-like kinase-1 (plk1) is a highly conserved serine/threonine kinase. Human plk1 gene is located at position 16p12 of the chromosome, encoding an mRNA of about 2.3 kb, and the molecular weight of the corresponding protein is about 67 kd. plk1 protein has a highly conserved catalytic domain at its N-terminal, and typically has three conserved domains called polo boxes at its C-terminal. The research indicates that plk1 plays a role in inducing DNA synthesis, checking and repairing DNA integrity, and preventing cell apoptosis. plk1 can also inhibit the transcriptional activity of p53 through phosphorylation, and further inhibit p53 from playing the functions of check-point protein and inducing cell apoptosis. p53 is a primary regulatory protein in G1 phase. The inhibitory effect of plk1 on cancer suppressor gene p53 induces continuous, even permanent G1 phase arrest. Further, plk1 is closely related to the occurrence and development of tumors. After the expression of plk1 gene is inhibited, cell proliferation will be inhibited and cell apoptosis will be promoted, thus tumor growth will be inhibited. plk1 can also regulate the inductive production of interferon (IFN) by inhibiting MAVS, thereby disrupting innate immunity.
plk1 highly expresses in most human tumor tissues, including breast cancer, liver cancer, lung cancer and colon cancer. The high expression of plk1 has a statistical correlation with the survival rate of tumor patients, and the expression level of plk1 in tumor tissues is also closely related to tumor metastasis and prognosis, which indicates that plk1 may play an important role during the generation and development of tumors and is a potential target site of antitumor drugs. Research progress also indicates that, blocking the expression of plk1 or inhibiting its kinase activity may effectively inhibit proliferation of tumor cells and mediate their apoptosis, while no obvious impact is exerted on normal cells. At present, a plurality of plk1 inhibitors in preclinical or clinical trial stage all exhibit characteristics of high drug properties and low toxicity.
Breast cancer is one of the most popular malignant tumors among women. Surgery, radiotherapy, chemotherapy and endocrinotherapy are four major clinical treatment means for breast cancer. Regarding most breast cancer patients, cancer cells may have already migrated to other tissues when breast cancer is determined during preliminary diagnosis, while chemotherapy as an important systemic intervention means plays an extremely important role in the treatment of breast cancer. At present, chemotherapeutic means mainly uses small molecular drugs and targeted macromolecular drugs. However, drug potency and consequent drug resistance are two major problems confronting the small molecular drugs commonly used during treatment of breast cancer, while a narrow range of applicable people is a major problem confronting targeted macromolecular drugs. Therefore, small interfering nucleic acid that can inhibit the expression of cancer gene as a substitute drug hopefully may solve the problems that cannot be solved by small molecular drugs and targeted antibody drugs. From several aspects including improvement of treatment effectiveness, drug resistance as well as reduction of toxic and side effect of antitumor drugs, the development of effective siRNA drugs, which are new pharmaceutical molecules that functions in a manner completely different from the action mechanisms of those mainstream drugs currently used in clinical application, has become an urgent need for current clinical application.